Malperfusion Syndrome Without Organ Failure Is 

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Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan. University School of Medicine ..... affect you, please call the Board office at (312) 202-. 5900.
Yang Hyun Cho, MD, PhD, Kiick Sung, MD, PhD, Wook Sung Kim, MD, PhD, Dong Seop Jeong, MD, PhD, Young Tak Lee, MD, PhD, Pyo Won Park, MD, PhD, and Duk-Kyung Kim, MD, PhD Departments of Thoracic and Cardiovascular Surgery and Medicine, Division of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Background. Malperfusion syndrome caused by acute type A aortic dissection is associated with high mortality. However, the impact of subclinical malperfusion is not clear. We reviewed surgical outcomes in acute type A dissection for the presence of clinical and subclinical malperfusion. Methods. From 1998 to 2012 at Samsung Medical Center, 268 consecutive patients had an emergency operation for acute type A dissection. We divided patients into three groups: clinical, subclinical, and no malperfusion. Clinical malperfusion was identified by signs or symptoms of organ dysfunction (n [ 36). Subclinical malperfusion was defined as laboratory evidence of organ hypoperfusion or imaging findings without signs or symptoms (n [ 40). Patients with no evidence of malperfusion were defined as having no malperfusion (n [ 192). Results. The mean patient age was 57.3 ± 13.8 years, and 141 patients (53%) were women. Antegrade selective cerebral perfusion was used in 213 patients (79%). Total arch

replacement was performed in 53 patients (20%). The average cardiopulmonary bypass time was 218.31 ± 72.17 minutes. Early mortality was 8% in all patients, 5% in the no-malperfusion group, 8% in the subclinical malperfusion group, and 25% in the clinical malperfusion group. Overall survival in the clinical malperfusion group was worse than in the subclinical (p [ 0.026) and nomalperfusion (p < 0.001) groups. Survival rates in the subclinical and no-malperfusion groups were not different (p [ 0.482). On multivariate Cox regression analysis, older age, longer cardiopulmonary bypass time, and clinical malperfusion syndrome were predictors of mortality. Conclusions. Mortality was not increased in asymptomatic patients with malperfusion by laboratory or imaging findings. Immediate operation before progression of organ malperfusion is still a valid option for patients with acute type A dissection.

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immediate operation. Although the symptoms and signs of organ ischemia are used for diagnosing malperfusion syndrome, imaging and laboratory findings are useful as supplemental information or for detecting early or subclinical malperfusion syndrome [10–12]. We hypothesized that subclinical malperfusion syndrome, which involves organ hypoperfusion with preserved function, would not affect surgical outcomes. We present the results of immediate surgical correction of type A dissection according to the preoperative status of organ hypoperfusion.

alperfusion syndrome is a catastrophic adverse event of aortic dissection [1–3]. The prognosis for patients with malperfusion syndrome is much worse than for patients without malperfusion. Acute type A aortic dissection involves the ascending aorta and easily produces cardiac tamponade, which requires an emergency operation [4, 5]. However, some studies advise delaying operation in cases of malperfusion syndrome [6–9]. If the operation is delayed, radiologic fenestration of the descending aorta is performed to create a large reentry. Delay of operation increases the risk of aortic rupture or cardiac tamponade and reentry during the intervention, leading to type B dissection after operation. The diagnosis of malperfusion syndrome can be challenging because acute type A dissection requires an

Accepted for publication March 5, 2014. Address correspondence to Dr Sung, Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea; e-mail: [email protected].

Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc

(Ann Thorac Surg 2014;98:59–64) Ó 2014 by The Society of Thoracic Surgeons

Patients and Methods Study Population We enrolled 268 consecutive patients who underwent operations for acute type A aortic dissection from November 1995 to December 2012 at Samsung Medical Center. Excluded were patients who had symptoms related to aortic dissection more than 2 weeks before presentation. Intramural hematoma was not considered to be a dissection. Patients with a diagnosis of acute type 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.03.026

ADULT CARDIAC

Malperfusion Syndrome Without Organ Failure Is Not a Risk Factor for Surgical Procedures for Type A Aortic Dissection

60 ADULT CARDIAC

CHO ET AL MALPERFUSION IN TYPE A DISSECTION

A dissection were not considered to have a contraindication for operation. Patients with cardiac arrest after the diagnosis of type A dissection were brought immediately to the operating room for surgical correction. All patients who agreed to surgical procedures, including permission given through the family, underwent emergency operations regardless of malperfusion syndrome. The Samsung Medical Center Institutional Review Board approved this study and waived the need for patient consent.

Operative Procedures The operative procedure was by standard median sternotomy. We routinely performed antegrade selective cerebral perfusion, using right axillary artery cannulation and balloon catheters during hypothermic circulatory arrest at 25 to 26 C. For cases of possible lower body ischemia, we cannulated both the right axillary and the femoral arteries. The adequacy of cardiopulmonary bypass perfusion was monitored by at least two arterial lines (right radial and femoral arteries), cerebral oximetry, and urine output. The aorta was opened from the sinotubular junction to the level of the aorta to be replaced. Proximal and distal anastomoses were treated by a previously described adventitial inversion technique or by a standard sandwich technique with the use of Teflon felt strips [13]. At the end of the cardiac procedure, peripheral circulation was evaluated. If no palpable pulse was detected or if systolic pressure of femoral artery was less than 60 mm Hg, an extraanatomic vascular bypass operation was performed. The extent of replacement was determined by the location of the intimal tear, patient age, and surgeon preference. Replacement was to the ascending aorta or hemiarch in 205 patients (77%), to the ascending and partial arch (replacement to the level of the innominate or left carotid artery) in 10 (4%), and to the ascending and total arch in 53 (20%). Among 49 concomitant root replacement procedures, 35 (71%) were Bentall procedures and 14 (29%) were valve-sparing root replacement procedures. Other

Ann Thorac Surg 2014;98:59–64

concomitant procedures were coronary artery bypass in 26 patients (10%), femorofemoral bypass in 7 (3%), and axillofemoral bypass in 7 (3%).

Malperfusion Syndrome Malperfusion syndrome was examined systemically by organ, specifically the coronary, neurologic, mesenteric, renal, and extremities. Clinical malperfusion syndrome was determined only when signs or symptoms of single or multiple organ failure were observed. We thoroughly reviewed the medical records, and patients were assigned to the clinical malperfusion group when two authors (Y.H.C. and K.S.) agreed on the malperfusion syndrome diagnosis. Asymptomatic patients with significant branch vessel stenosis by echocardiography or computed tomography, laboratory findings of organ hypoperfusion, or hypoenhancement on computed tomography were assigned to the subclinical malperfusion group [14–16]. Patients with no evidence of malperfusion were assigned to the no-malperfusion group. The definitions used for grouping are given in Table 1.

Endpoints and Follow-Up The primary endpoints were early and late mortality. Early mortality was defined as death within 30 days after operation or death during the same admission. Patients had regular follow-up at the outpatient clinic for 1 to 3 months. Follow-up was closed on July 31, 2013. The mean follow-up duration was 54 months, and the longest was 206 months.

Statistical Analysis Measurements are expressed as means  standard deviation (SD) or as frequencies and proportions. Intergroup comparisons used a c2 test (Pearson’s c2 and Fisher’s exact tests) for categorical variables and one-way analysis of variance for continuous variables. All tests were two-tailed. Survival analysis used the Kaplan-Meier method and log-rank tests. Cox regression analysis

Table 1. Definition of Malperfusion Syndrome Organs

Clinical Malperfusion Group

Coronary

Evident ST change in EKG and regional wall motion abnormality in echocardiography

Neurologic

Focal or generalized neurologic deficit unrelated to shock

Mesenteric

Abdominal pain with tenderness and rebound tenderness

Renal

Anuria or severe oliguria (urine output 0.8 ng/mL or coronary flow compromise on transesophageal echocardiography or computed tomography True lumen collapse >70% or decreased contrast enhancement of right or left carotid artery on computed tomography Decreased contrast enhancement of abdominal organs on computed tomography with abnormal liver or pancreatic enzyme Increase in creatinine of 50% from baseline or creatinine >1.5 mg/dLa with decreased contrast enhancement of both kidneys on computed tomography True lumen collapse >70% of subclavian, femoral, or proximal arteries on computed tomography

CHO ET AL MALPERFUSION IN TYPE A DISSECTION

determined predictors of long-term clinical outcomes. Variables with p values less than 0.2 in univariate analysis were entered into multivariate analysis. A p value of less than 0.05 was considered statistically significant. Statistical analysis used SPSS version 21.0 (SPSS, Chicago, IL).

Results Baseline Characteristics and Operative Results The patient characteristics by groups are shown in Table 2. The mean age was 57.3  13.8 years (range, 21–84 years), and 141 patients were women (53%). The nomalperfusion group had a higher percentage of women than did the other groups. All preoperative laboratory results were significantly elevated in both the clinical and the subclinical malperfusion groups compared with the no-malperfusion group. However, the laboratory findings were not different between the clinical and subclinical malperfusion groups (Table 2). Most patients had antegrade selective cerebral perfusion during systemic hypothermic circulatory arrest (n ¼ 213, 79%). Aortic root replacement was performed in 49 patients (18%) and total arch replacement in 53 (20%). The average times were 218.31  72.17 minutes for cardiopulmonary bypass, 137.4  57.12 minutes for aortic crossclamp, and 54.34  30.91 minutes for total circulatory arrest. Early mortality was 25% in the clinical malperfusion group (p ¼ 0.037 versus subclinical malperfusion group; p < 0.001 versus no-malperfusion group). However, early mortality was not higher in the subclinical malperfusion group than in the no-malperfusion group (8% vs 5%, p ¼ 0.566). The postoperative morbidities of low cardiac output syndrome, reoperation for bleeding, tracheostomy, gastrointestinal adverse event, stroke, and deep sternal wound infection were not different among groups. Acute kidney injury requiring dialysis was more common

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in the clinical malperfusion group than in the nomalperfusion group (p < 0.001) (Table 3). The estimated 5-year survival rates were 67% in the clinical malperfusion group, 82% in the subclinical malperfusion group, and 86% in the no-malperfusion group. The overall survival in the clinical malperfusion group was worse than in the subclinical and no-malperfusion groups (p ¼ 0.026 and p < 0.001, respectively). However, the survival rates in the subclinical and no-malperfusion groups were not different (p ¼ 0.482) (Fig 1).

Predictors of Mortality By multivariate Cox regression analysis, older age, longer cardiopulmonary bypass time, and clinical malperfusion syndrome were predictors of mortality. Female gender, diabetes mellitus, hypertension, coronary artery disease, Marfan syndrome, preoperative cardiopulmonary resuscitation, previous cardiac operation, total arch replacement, aortic root replacement, long aortic cross-clamp time, and subclinical malperfusion syndrome were not significant predictors of mortality (Table 4).

Comment Malperfusion syndrome in type A dissection is a significant predictor of poor surgical outcome. Therefore, physicians often try to identify malperfusion syndrome before operation and to delay operating until interventional fenestration has been performed [6–9, 17]. This strategy has two potential problems. One problem is that delaying the operation might increase the chance of aortic rupture and the duration of malperfusion syndrome until the fenestration procedure is performed. This delay could result in death or worsened condition. Ultimately, delay might eliminate the chance of surgical repair. The second problem is that a large fenestration made for false lumen decompression might become the entry site of a later type

Table 2. Baseline and Operative Characteristics Characteristics Age (SD) Female (%) Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%) Marfan syndrome (%) Preoperative cardiopulmonary resuscitation (%) Previous cardiac operation (%) Preoperative laboratory results Troponin T, ng/mL (SD) AST, unit/L (SD) ALT, unit/L (SD) Amylase, unit/L (SD) Creatinine, mg/dL (SD)

CM Group n ¼ 36

SM Group n ¼ 40

NM Group n ¼ 192

p Value

55.15 15 21 2 2 4 3 1

(15.14) (42) (58) (6) (6) (11) (8) (3)

55.38 12 23 1 1 4 4

(15.28) (30) (58) (3) (3) (10) (10) 0

58.10 114 117 9 4 18 8 6

(13.20) (60) (61) (5) (2) (10) (4) (3)

0.319 0.001 0.898 0.785 0.487 0.947 0.257 NA

5.14 108.14 67.14 68.44 1.50

(13.23) (214.79) (110.58) (49.05) (0.85)

16.79 122.41 78.87 92.24 1.81

(55.16) (268.51) (141.58) (76) (1.78)

0.38 45.03 33.15 52.81 0.95

(2.42) (66.61) (41.69) (20.99) (0.29)

0.013 0.001 0.001 0.049